Genetic variation in FCER1A predicts peginterferon alfa-2a-induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B

J Viral Hepat. 2019 Sep;26(9):1040-1049. doi: 10.1111/jvh.13107. Epub 2019 Jul 23.


In a multicentre, genome-wide association study to identify host genetic factors associated with treatment response in adult chronic hepatitis B patients, genotype data were obtained by microarray analysis from 1669 patients who received peginterferon alfa-2a for ≥ 24 weeks with/without a nucleos(t)ide analog. Treatment response was assessed at least 24 weeks post-treatment, using serological and/or virological endpoints. Thirty-six single-marker analyses and a gene-by-gene analysis were conducted. No single nucleotide polymorphisms (SNPs) achieved genome-wide significance (P < 5 × 10-8 ) in single-marker analyses, but suggestive associations (P < 1 × 10-5 ) were identified for 116 SNPs. In gene-by-gene analyses, one gene, FCER1A (rs7549785), reached genome-wide significance (P = 2.65 × 10-8 ) in East Asian patients for hepatitis B surface antigen (HBsAg) clearance, with a moderate effect size (odds ratio = 4.74). Eleven of 44 carriers (25%) of the A allele at rs7549785 achieved HBsAg clearance compared with 69/1051 (7%) noncarriers. FCER1A encodes the alpha subunit of the immunoglobulin E receptor. In a post hoc analysis of a homogenous patient subset, the strongest intragenic association was for rs7712322 (POLR3G, P = 7.21 × 10-7 ). POLR3G encodes the G subunit of the polymerase (RNA) III enzyme, involved in sensing and limiting infection by intracellular bacteria and DNA viruses, and as a DNA sensor in innate immune responses. FCER1A (rs7549785) and possibly POLR3G (rs7712322) are shown to be associated with peginterferon alfa-2a response in adult patients with chronic hepatitis B. Independent confirmation of these findings is warranted ( number NCT01855997).

Keywords: chronic hepatitis B; genetic variation; peginterferon alfa-2a; response.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antiviral Agents / therapeutic use*
  • Asian People
  • Drug Therapy, Combination
  • Female
  • Genetic Variation
  • Genome-Wide Association Study
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / ethnology*
  • Hepatitis B, Chronic / genetics*
  • Humans
  • Interferon-alpha / therapeutic use*
  • Male
  • Microarray Analysis
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide
  • RNA Polymerase III / genetics
  • Receptors, IgE / genetics*
  • Receptors, IgE / immunology
  • Recombinant Proteins / therapeutic use


  • Antiviral Agents
  • FCER1A protein, human
  • Hepatitis B Surface Antigens
  • Interferon-alpha
  • Receptors, IgE
  • Recombinant Proteins
  • Polyethylene Glycols
  • POLR3G protein, human
  • RNA Polymerase III
  • peginterferon alfa-2a

Associated data